tbuckley/cabot-search huggingface dataset:
Symptomatic adverse events in lung cancer clinical trials included in US drug labels from 2015 to 2021 to inform patient-reported outcomes.
Authors: Erica Horodniceanu, Tejaswi Datla, Meena N. Murugappan, Erin A. Larkins, Harpreet Singh, Vishal Bhatnagar, Paul Kluetz
Journal: Journal of Clinical Oncology (2023)

e13642 Background: FDA recommends assessing expected symptomatic adverse events (symAEs) as a core patient-reported outcome (PRO) in cancer clinical trials (CTs). Several core PRO symptom lists exist that measure the same symptoms across trial contexts; however, many were developed in an era when cytotoxic chemotherapy was the main mechanism of action (MOA). To further research relevant PROs in modern cancer CTs, we identified common symAEs from recently approved lung cancer drugs across MOAs. Methods: We identified lung cancer drug approvals from 2015 through 2021 using an FDA database. The drug US Prescribing Information (PI) was used to extract indication, MOA, CT information, and all-grade symAEs reported in ≥20% of patients in the investigational arm. To improve symAE attribution to the drug, we limited analysis to CTs with a monotherapy investigational arm. We determined the most common symAEs based on the number of CTs reporting a specific symAE in ≥20% of patients. Results: Of 54 approvals identified, 31 lung cancer CTs (30 for NSCLC, 1 for SCLC) with monotherapy investigational arms were included, with AE data from 9,829 patients. Drug MOAs were classified broadly as growth pathway inhibitors (GPI) for 21 CTs (68%), immunotherapy (IO) for 9 CTs (29%), and cytotoxic chemotherapy for 1 CT (3%). Most common symAEs are presented in Table 1 (truncated to symAEs in ≥9 CTs, based on All CTs). In comparing MOAs, symAEs reported at ≥20% incidence in ≥5 GPI CTs but in no IO CTs included: diarrhea (76% of GPI CTs), edema (38%), nail toxicity/paronychia (29%), vomiting (29%), stomatitis (29%), and dry skin (24%). Fifteen other symAEs were reported at ≥20% incidence in ≥3 GPI CTs, but in no IO CTs [data not shown]. Conclusions: While there were several common symAEs across lung cancer CTs, our analysis using AE data in PIs of recently approved drugs showed important variability between CTs and broad GPI and IO groups, demonstrating that consideration of MOA and expected toxicity are important for ensuring relevant high frequency symAEs are included as PROs. Final selection of expected symAEs from a PRO item library is context dependent, requiring consideration of all available clinical data and patient input.[Table: see text]
The mechanism of exosome delivered circ-PDE7B promoting liver metastasis of breast cancer.
Authors: Wang Dandan, Jinhai Tang
Journal: Journal of Clinical Oncology (2023)

e13016 Background: According to “seed and soil” hypothesis, tumor microenvironments have major effects on the survival and metastasis of cancers, including breast cancer. Importantly, exosomes are believed to partake in cellular communications through delivering oncogenic ncRNAs (including circRNAs) to the recipient cells and tumor microenvironment, which resulting in distant metastasis. Unfortunately, exosomes delivering circRNAs from breast cancer cells still remained many potential functions that are not completely understood in the progression of liver metastasis of breast cancer. This study aims to provide a theoretical basis to use stable exosomal circRNAs as new biomarkers and target spot for the liver metastasis of breast cancer. Methods: A strategy combining RNA-sequencing technique, RT-qPCR and bioinformatic analysis were used to determine the level of differential expressed circRNAs in tissue exosomes (n=5) and serum exosomes samples (n=5) from liver metastatic breast cancer patients compared with healthy person. The expression of circPDE7B was also detected in tumor tissues (n=10) from liver metastatic patients compared with healthy person, breast cancer cell lines (MDA-MB-231), high-liver metastatic cell lines (LM-MDA-MB-231), exosome from MDA-MB-231 (231/exo) and from LM-MDA-MB-231 (LM-231/exo) by RT-qPCR. In animal experiments, exosomes (enriched in circPDE7B) were injected from tail vein for 24h, follow up with injection with LM-MDA-MB-231 cells, then, fluorescence imaging and pathology showed the metastasis in liver. Results: Isolated serum exosomes were characterization by transmission electron microscope (TEM) and Nanosight 300 (NTA 300) system. We profiled the circRNAs in the tissue and serum exosomes samples from liver metastatic patients and healthy person by RNA sequencing and detected 332 significantly differentially-expressed circRNAs. After bioinformatic analysis with GEO database, circPDE7B was chose to further study. RT-qPCR results showed that higher expression of circPDE7B in liver metastatic tissue and LM-MDA-MB-231, also in LM-231/exo. Moreover, overexpressed circPDE7B in exosomes from breast cancer changes premetastatic microenvironment of the liver microenvironment, which can promote the occurrence of breast cancer liver metastasis. Conclusions: The expression of circPDE7B was found significantly upregulated in tissue and serum exosomes from liver metastatic breast cancer patients. Moreover, circPDE7B could promote liver metastasis of breast cancer. Therefore, this study provides a fresh perspective on novel therapeutic targets and potential biomarkers for liver metastasis from exosomal circRNAs.
Real-world multicentre analysis of patients with hepatocellular carcinoma (HCC) treated with atezolizumab and bevacizumab (A+B): Efficacy, esophagogastroduodenoscopy (EGD) uptake and bleeding complications.
Authors: Cha Len LEE, Mark Freeman, Conor O'Donnell, Gordon Taylor Moffat, Ekaterina Kosyachkova, Hanna Lyubetska, Brandon M. Meyers, Vallerie Lynn Gordon, Philip Q. Ding, Aileigh Kay, Roxana Bucur, Winson Y. Cheung, Jennifer J. Knox, Vincent C. Tam
Journal: Journal of Clinical Oncology (2023)

4105 Background: The IMbrave150 trial established A+B as a standard of care for HCC and an EGD within 6 months (mos) of starting treatment to detect esophagogastric varices and prevent bleeding complications was advised. However, the value of performing EGD in all patients (pts) is unknown. Methods: We conducted a retrospective analysis of all HCC pts treated with A+B between July 2020 to August 2022 at 5 cancer centres from the Canadian provinces of Ontario, Alberta and Manitoba (members of the HCC-CHORD Consortium). Pts characteristics and treatment history including efficacy, EGD details and bleeding events were collected. Overall survival (OS), progression-free survival (PFS) and response rate (RR) were calculated. A comparative analysis was conducted to compare the correlation between the EGD uptake and bleeding events. Results: A total of 112 pts were identified (median age 66 years, 87% male, 24% East Asian, 67% liver cirrhosis, 33% HCV, 25% HBV, 15% NASH, 23% BCLC B, 71% BCLC C, 91% Child-Pugh A, 29% main portal vein invasion, 45% ALBI grade 1 and 54% ALBI grade 2). Prior to systemic, 61% had locoregional therapies. 90% received A+B as first-line therapy, while 9% received it as second-line and 1% as third-line. Outcomes of pts treated with A+B are shown. Before starting A+B, 78 pts (70%) had completed an EGD within 6 mos. Of these, 32 pts (41%) had evidence of varices on EGD, and 15 (20%) required treatment with either banding or beta-blockers. All bleeding events in this population was 15% (n=17). Bleeding rates in the EGD and non-EGD groups were 18% (n=14) and 9% (n=3), respectively. Bleeding adverse events were 5%(n=6) gastrointestinal vs 10%(n=11) non-gastrointestinal (6 epistaxis, 1 ecchymosis, 1 periodontal and 3 unspecified). The GI bleeding rates in the EGD and non-EGD groups were 6% (n=5) and 3% (n=1). Conclusions: Outcomes of HCC pts treated with A+B in Canada are comparable to those observed in the IMbrave150 trial. Our study detected and treated varices at twice the rate of the IMbrave150 trial among the EGD group, reflecting real-world treatment of a high-risk population. Yet, pts who had no EGD before starting A+B, presumably due to a low risk of portal hypertension based on physicians’ judgement, did not experience more bleeding/GI bleeding than those who had an EGD. This supports the approach of selective EGD prior to A+B, and more guidelines are needed in this area. Outcomes and response rate of patients(pts) treated with Atezolizumab with Bevacizumab in this study. [Table: see text]
Immune checkpoint inhibitor (ICI) therapy in glioblastoma: Institutional experience at the Massachusetts General Hospital (MGH).
Authors: John Yohan Rhee, Kun Wei Song, Isabel Arrillaga-Romany, Deborah Anne Forst, Justin T. Jordan, Ina Ly, Scott Randall Plotkin, Nancy Wang, Michael Parsons, Elizabeth R Gerstner, Jorg Dietrich
Journal: Journal of Clinical Oncology (2023)

2065 Background: Immune checkpoint inhibitors (ICI) have resulted in promising outcomes in systemic cancer but response in glioblastoma (GBM) has not met early expectations based on early clinical trial results. Conflicting data exists regarding the incidence of pseudoprogression after ICI in brain tumors. Here, we present our institutional experience of the radiographic response following ICI therapy in GBM both at initial diagnosis and recurrence. Methods: We retrospectively identified IDH-wildtype GBM (per 2021 WHO criteria) patients treated either at time of initial diagnosis or at recurrence with nivolumab, pembrolizumab, or durvalumab between 2015 and 2022 at MGH. Overall radiographic and clinical responses after initiation of ICI were assessed in both groups. Results: 56 pts (18 female, 38 male) were identified (average age 58.6). Eight (14.3%) patients had ICI-related non-hematological toxicities, including granulomatosis folliculitis, arthritis and myositis, headache, acneiform rash, transaminitis, and gastritis). Four (7.1%) of the eight patients had to discontinue treatment due to ICI-related severe toxicity (hepatitis and/or gastritis) and were not included in the final response assessment. Of the remaining 52 patients, none had evidence of pseudoprogression related to ICI. We did not identify any complete response (CR) or partial response (PR) secondary to ICI monotherapy. In the 13 patients treated at initial diagnosis, the following radiographic responses were seen: CR=0, PR=0, stable disease (SD)=5 (38.5%), and progressive disease (PD)=8 (61.5%). In the 39 patients treated at disease recurrence, the responses were: CR=0, PR=4 (10.3%), SD=10 (33.3%), PD= 22 (56.4%). Noteworthy, all patients with PR were concurrently treated with bevacizumab. Conclusions: 0/52 patients showed radiographic response after ICI monotherapy. While treatment was overall tolerated, ICI therapy was discontinued due to toxicity in 7% of patients. Pseudoprogression attributable to ICI was not seen in any of the patients treated.
Outcomes on the hematology malignancy hospitalist service: A model for inpatient care.
Authors: Alaina J. Kessler, Aarti Sonia Bhardwaj, Carol Kisswany, Tianxiang Sheng, Lauren Scott, Olga Prystupa, Maria Reyna, Marina Kremyanskaya, Cardinale B. Smith
Journal: Journal of Clinical Oncology (2023)

1536 Background: The use of oncology hospitalists has been shown to improve quality outcomes among hospitalized patients, though there is limited data on the use of hospitalists to care for patients with hematologic malignancies. The Hematology Malignancy Hospitalist Service (HMHS) was created in efforts to decrease patient volume on the primary hematology malignancy services at an academic hospital. Patients with active oncologic issues requiring specialty oncology management were cared for by oncologists on the primary leukemia, lymphoma, and myeloma services while patients with acute medicine-related issues were cared for by medicine hospitalists on HMHS. Methods: Criteria were established based on level of acuity and reason for admission to HMHS, which was comprised of a hospitalist attending and nurse practitioner. New admissions to HMHS were evaluated by the primary hematology malignancy service team as consultants and remained involved in patient care as deemed appropriate. Oncology attendings continued to care for patients on the primary leukemia, lymphoma, and myeloma services. We conducted a retrospective analysis from 6/28/21 through 6/30/22 excluding 1/2/22 to 2/6/22 when HMHS was paused due to the COVID Omicron surge. We compared length of stay (LOS), discharge before noon (DBN), and 30-day readmission rates of patients admitted to the HMHS service and those admitted to the primary services to assess for differences in outcomes. Results: There were a total of 95 (12%) admissions to HMHS and 669 (88%) to the primary services; 35.6% patients were white, 21.7% Black, and 10.3% Asian and 26.3% patients identified as Hispanic. The average age was 61.6 years. The average LOS in days was 9±9.09, 16.03±14.96, 11.41±14.88, and 12.68±11.40 (p = 0.005) for patients admitted to HMHS, leukemia, lymphoma and myeloma services, respectively. DBN on HMHS (6%) was similar to the leukemia service (6%) and improved compared to the lymphoma service (11%) and myeloma service (7%); p = 0.66. The 30-day readmission rate was also improved on HMHS (12%) compared to leukemia (21%), lymphoma (21%), and myeloma (18%); p=0.25. Conclusions: The development and implementation of a medicine hospitalist-driven hematology malignancy service significantly improved LOS without a negative impact on 30-day readmission rates when compared to a primary hematology malignancy service model. The addition of medicine hospitalists to the inpatient care of patients with hematologic malignancies demonstrates improvement in healthcare utilization. This is an important area for future evaluation to determine the most appropriate patients to admit to these services and assess other important outcomes.
<i>MTHFR</i> polymorphisms and neurotoxicity and overall survival after methotrexate-based therapy in primary CNS lymphoma.
Authors: Philipp Karschnia, Sylvia C. Kurz, Priscilla Kaliopi Brastianos, Sebastian F. Winter, Amanda Gordon, SooAe Jones, Michelle Pisapia, Naema Nayyar, Joerg Tonn, Tracy Batchelor, Scott Randall Plotkin, Jorg Dietrich
Journal: Journal of Clinical Oncology (2023)

2079 Background: The folate-antagonist methotrexate (HD-MTX) is an integral to induction chemotherapy for primary CNS lymphoma (PCNSL); however, it can be associated with toxicities, including injury to cerebral white matter known as leukoencephalopathy. Methylenetetrahydrofolate Reductase (MTHFR) is involved in intracellular folate metabolism, and MTHFR polymorphisms may affect CNS-specific side effects of HD-MTX. Here, we evaluated the possible association of MTHFR polymorphisms an HD-MTX related CNS toxicity. Methods: We retrospectively searched our institutional database at the Massachusetts General Hospital for newly diagnosed PCNSL patients treated with HD-MTX (without use of radiotherapy or intrathecal chemotherapy). MTHFR polymorphisms were correlated with evolution of leukoencephalopathy over a time period of five years and patient outcomes. ROC curves were generated to estimate the diagnostic ability of specific MTHFR genotypes. Survival was calculated using Kaplan-Meier survival analysis and log-rank test. The significance level was set at p ≤ 0.05. Results: Among 68 PCNSL patients, MTHFR polymorphisms were found in 60 individuals (88.2%; 677C&gt;T: 29 patients, 1298A&gt;C: 18 patients, combined 677C&gt;T &amp; 1298A&gt;C: 13 patients). Neither MTX clearance nor disease response to HD-MTX was affected by specific genotypes, and complete response was achieved in 72.1% of patients by induction with HD-MTX-based therapy. However, the 1298A&gt;C genotype was associated with increased frequency and severity of leukoencephalopathy over time (χ 2 = 7.43). Such genotype predicted treatment-induced leukoencephalopathy with a sensitivity of 71.0%% and a specificity of 62.2% (ROC: p = 0.019). While progression-free survival did not differ in genotype-based subgroups, overall survival was significantly lower when the 1298A&gt;C genotype was present. Conclusions: The MTHFR 1298A&gt;C genotype may serve to identify PCNSL patients at elevated risk for HD-MTX-induced leukoencephalopathy. This was associated with reduced overall survival, potentially due to decreased functional status in patients less suitable for aggressive subsequent therapies.
Improving cancer care in underserved regions through technology-enabled patient-reported outcomes.
Authors: Kingsley Ndoh, Christian Ruchaho Ntizimira, Irene Dankwa-Mullan, Theoneste Maniragaba
Journal: Journal of Clinical Oncology (2023)

1520 Background: The growing cancer burden in Africa is a major public health challenge. There were 8,944 new cases in Rwanda, with over 6,044 deaths reported in 2020. Unfortunately, there are only 13 oncologists in Rwanda for a population of 13 million people. The use of artificial intelligence (AI) tools and digital health in cancer treatment has the potential to mitigate the oncology workforce shortages, support clinical decision-making, and increase access to care. Hurone AI is a Seattle MedTech startup building culturally sensitive AI applications to address the oncologist-patient gaps and improve drug safety in underserved populations. Hurone’s premier application, Gukiza, launched at the Rwanda Cancer Center in 2022 to conduct beta testing. Gukiza is a remote patient monitoring system that ensures patients can report side effects or symptoms from their phones and oncology care teams can get real-time treatment insights and provide timely and effective care. Methods: Hurone received ethical approval from the Rwanda National Ethical Committee to launch a pilot in September 2022. An initial 45 breast cancer patients aged 20 – 65 who were either newly diagnosed or on active treatment were recruited. Each patient periodically received prompts that asked them about side effects and to score the degree of severity. The questions were adapted from the NCI’s adverse events repository. Gukiza analyzed each response and presented a visual analysis of each patient, enabling the cancer care team to send text-based interventions to the patient’s phone. Potential emergencies are flagged and sent emergency numbers to call. Through Amazon’s cloud analytic tools, Gukiza provides treatment insights to support oncologists' clinical decisions. Results: Results are summarized. Conclusions: Resource-appropriate digital technologies can be a useful tool in mitigating adverse events during cancer treatment and increasing access to timely care for patients. The data built in such systems can be a useful resource to individualize and improve cancer care and treatment outcomes.[Table: see text] [Table: see text]
Remote evaluation of NAVIFY Oncology Hub using clinical simulation.
Authors: Jack Halligan, Ethan Goh, Ernest N. Lo, Delphine Chabut, Matthew Stewart Prime, Saira Ghafur
Journal: Journal of Clinical Oncology (2023)

e13622 Background: Clinical workflow is critical for the efficient and safe delivery of patient care. NAVIFY Oncology Hub is a clinical workflow solution that provides clinicians with a comprehensive view of a patient’s clinical journey and aims to enable effective and efficient care decisions in oncology care. This study explored the use of remote clinical simulation to assess the usability, efficiency, and cognitive burden associated with using NAVIFY Oncology Hub. Methods: Twenty seven (27) board-certified oncologists were recruited to participate in remote evaluation sessions conducted via teleconference. Participants were instructed to review and synthesize clinical information from 10 synthetic breast cancer cases using NAVIFY Oncology Hub (case order was randomized). After completing the exercise, participants answered a survey which included the system usability scale (SUS), Likert-scale questions designed for participants to self-report the efficiency of completing each task, and the NASA Task Load index (to assess cognitive burden). The survey and a short interview was also used to gather structured feedback on the solution, patient cases, and study methods. Results: NAVIFY Oncology Hub scored an “excellent” 82 on the system usability scale (SUS). Most participants (67%) indicated that they would be likely to use the solution in their clinical practice, with approximately half (48%) reporting they would recommend it to a colleague. The majority of participants (96%) said they were “a lot more efficient” or “somewhat more efficient” when using NAVIFY Oncology Hub to review patient information. The majority of participants (78%) felt it would be “significantly better” or “somewhat better” than their existing solution at facilitating patient discussion and coordinating care. On the NASA Task Load Index survey, the majority of participants (63%) required low or very low levels of mental demand, temporal demand, and effort to successfully complete tasks using NAVIFY Oncology Hub. The majority of participants (91%) felt the synthetic patient cases were either ‘very similar’ or ‘somewhat similar’ to cases seen in routine clinical practice, and that the tasks completed during the sessions were ‘very similar’ or ‘somewhat similar’ to their clinical practice. Conclusions: This novel clinical simulation study shows early evidence that NAVIFY Oncology Hub has high usability, potential to increase overall efficiency and reduce cognitive burden on oncologists compared to contemporary EHR systems. Clinical trial information: NCT05478135 .
Inter-regional differences of authorship in secondary analyses of solid malignancies.
Authors: Yazan Hamadneh, Jawad Alrawabdeh, Muntaser Al Zyoud, Nada Wael Odeh, Marah Alzubi, Samer Al Hadidi
Journal: Journal of Clinical Oncology (2023)

e13661 Background: With the increasing number of clinical trials and data availability in recent years, the number of secondary analyses had subsequently increased at a global level. However, the results of such analyses must be interpreted carefully. Our study aimed to study the differences of secondary analyses based on the country of residence of the first author. Methods: We searched OVID database for articles subgroup analyses from the year 2000 until Feb 15, 2022. post-hoc, subgroup, secondary, cancer, tumor, breast, colorectal were some of the terms used in the search. Original trials, observational and secondary analyses of cohort studies were excluded. The country of the first author was used for categorizing the articles. Results: 1491 articles were included in final analysis. The first authors of 646 articles were from North America (43.9%), 476 articles from Europe (32.4%), 258 articles from East Asia (17.6%), and 86 articles from the rest of the globe (5.9%). There was a significant increase in the number of secondary analyses from East Asia especially in the last 4 years (&lt;.001). In addition, East Asian secondary analyses were more likely to have had medical writing assistance compared to other regions (&lt;.001). North American contribution to secondary analyses has been decreasing over the years (&lt;.001). European analyses and analyses from the rest of the world didn’t have a significant increase over the years. Although European publication were less likely to be funded, those that were funded had a higher chance of being funded by pharmaceutical companies in comparison to the different regions (&lt;.001). International trials that included US and non-US participants were more likely to be funded by pharmaceutical companies, had medical writing assistance, and had a higher percentage of authors with conflicts of interest than trials that only included US participants or non-US participants (&lt;.001). Conclusions: The results show that there was an increase in secondary analyses especially from the East Asian region and those secondary analyses of international trials are highly funded and supported by pharmaceutical companies. [Table: see text]